The present invention relates to the use of derivatives of tetrahydropyridines (or 4-hydroxypyperidines)butylazoles of general formula (I), as well as their physiologically acceptable salts, in the preparation of medicaments useful in human and/or veterinary therapy for the treatment of acute pain, neuropathic pain and nociceptive pain, either alone or in combination with other analgesics, producing in this case a synergy.
In our patent application WO 96/04287 compounds of general formula (I) are disclosed 
that have an affinity for the cy and 5HT1A receptors, and which are claimed as medicaments useful for the treatment of anxiety, psychosis, epilepsy, convulsion, amnesia, cerebro-vascular diseases and senile dementia.
We have now discovered that the compounds of general formula (I), as well as their pharmaceutically acceptable salts, are especially useful for the preparation of medicaments, useful in human and/or veterinary therapy for the prophylaxis, alleviation or curing of acute pain, neuropathic pain and nociceptive pain, either alone or in combination with other analgesics, giving rise in this case to a synergy.
The present invention relates to the use of derivatives of tetrahydropyridines (or 4-hydroxypyperidine)butylazoles of general formula: 
where
R1, R2 and R3 are either identical or different and represent a hydrogen atom, a C1-C4 alkyl group, a trifluoromethyl radical, a hydroxyl or alkoxyl radical, and furthermore, two adjacent radicals can form part of an six-member aromatic ring; A represents a carbon atom and the dotted line represents an additional bond, or A represents a carbon atom bound to a hydroxyl group (Cxe2x80x94OH) and the dotted line represents the lack of an additional bond;
Z1 represents a nitrogen atom or a substituted carbon atom that can be represented by Cxe2x80x94R4;
Z2 represents a nitrogen atom or a substituted carbon atom that can be represented by Cxe2x80x94R5;
Z4 represents a nitrogen atom or a substituted carbon atom that can be represented by Cxe2x80x94R7;
with the condition that Z1, Z2 and Z4 taken together can represent, at most, two nitrogen atoms; and
R4, R5, R6 and R7, are identical or different and represent a hydrogen atom, a halogen atom, a C1-C4 alkyl group, an aryl or substituted aryl group, or two adjacent radicals can form part of a six-member aromatic ring;
or one of their physiologically acceptable salts, in the elaboration of a medicament for the treatment of acute pain, neuropatic pain or nocipeptive pain in mammals, including man.
The term xe2x80x9ca halogen atomxe2x80x9d represents a fluorine, chlorine or bromine atom.
The term xe2x80x9caryl or substituted arylxe2x80x9d represents a phenyl radical or a phenyl radical substituted by halogen.
The term xe2x80x9calkoxylxe2x80x9d represents a methoxyl or ethoxyl radical.
The term xe2x80x9cG1-G4 alkylxe2x80x9d represents a straight chain or branched radical that is based on a saturated hydrocarbon of 1 to 4 atoms of carbon, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl y tercbutyl for example.
Physiologically acceptable salts of the compounds of general formula (I) refer both to salts formed with inorganic acids and organic acids, in particular, to salts of hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, acetic acid, lactic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, malic acid, tartaric acid, citric acid, ascorbic acid, maleic acid, benzoic acid, phenylacetic acid, cinamic acid, salicylic acid and alkyl, cycloalkyl or arylsulphonic acids.
The use of derivatives of general formula (I) for the treatment of pain refers to the use of analgesics in clinical practice. The term acute pain includes, but is not limited to, headache, arthritis, muscular tension or dysmenorrhea. The term neuropathic pain includes, but is not limited to, chronic back pains, pain associated with arthritis, herpes, pain associated with cancer, pain of a phantom limb, pain during childbirth or neuropathic pain resistant to opoids. The term nociceptive pain includes, but is not limited to, post-operation pain, dental pain, pain arising from surgery, pain caused by serious burns, post-natal pain or pain related with the genitourinary tract.
The derivatives of general formula (I) can be prepared according to the procedures disclosed in our patent application WO 96/04287.
In human therapy, the dosage administered of the compounds of the present invention varies as a function of the seriousness of the affliction to be treated. Normally the dosage will lie between 1 and 100 mg/day. The compounds of the invention can be administered as the only active ingredient or in conjunction with another analgesic in 2 proportion of one part of compound of general formula (I) with around one to ten parts of the other analgesic, with the aim of provoking a synergy. Other analgesics include, but are not limited to, non-steroid anti-inflammatory compounds such as aspirin or indomethacine, other analgesics such as paracetamol, narcotic analgesics or related compounds such as morphine, meperidine or pentazocine. The compounds of the invention, with a suitable pharmaceutical formulation, are administered by different routes, such as orally, transdermically, parenterally, subcutaneously, intranasally, intramuscularly or intravenously. Pharmaceutical compositions that contain compounds of general formula (I) are disclosed in our patent application WO 96/04287.